The Effectiveness of Nicotine Replacement Therapy in Light Versus Heavier Smokers.

INTRODUCTION: The prevalence of light smoking has increased in North America; however, research on the effectiveness of current treatments in this subpopulation of smokers is limited. We compared quit outcomes between light (1-10 cigarettes per day [CPD]) versus heavier smokers (>10 CPD) enrolled in a treatment program at their primary care clinic. AIMS AND METHODS: This secondary analysis analyzed 45 087 participants (light smokers [n = 9861]; heavier smokers [n = 35 226]) enrolled in a smoking cessation program between April 2016 and March 2020. The program offered cost-free nicotine replacement therapy (NRT) plus in-person counseling. Type, dose, and duration of NRT treatment were personalized. Data were collected at baseline, and at 6 months following enrollment to assess 7-day point prevalence abstinence (PPA), the primary outcome variable of interest. Logistic regression models were used for analyses. RESULTS: Seven-day PPA at 6 months was significantly higher among light smokers (30.6%) than heavier smokers (26.0%; odds ratio = 1.25, 95% confidence interval = 1.18-1.33, p < .001). Heavier smokers were prescribed more weeks of NRT than light smokers (B = 0.82, 95% confidence interval = 0.64-1.0, p < .001). The association between smoking cessation and daily NRT dose did not differ between groups (p = .98). However, a stronger positive relationship between the number of clinic visits attended and 7-day PPA was found among heavier smokers in comparison to light smokers (p < .001). All findings remained significant after adjusting for baseline variables. CONCLUSIONS: There is a paucity of scientific literature on the effectiveness of NRT for light smokers. Our findings suggest that individualized doses of NRT may be helpful in these subpopulations, and highlight the different treatment needs of light smokers. IMPLICATIONS: Current clinical guidelines do not provide formal recommendations for light smokers who want to quit smoking. Similar to heavy smokers, light smokers are at substantial risk for many adverse health problems. As such, it is important to understand what treatment options are effective in assisting light smokers to quit smoking. Findings from this study support the use of personalized treatment for all smokers who are interested in quitting smoking, including light smokers.

Influence of GABAA and GABAB receptor activation on auditory sensory gating and its association with anxiety in healthy volunteers.

BACKGROUND: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). AIMS/METHODS: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety. RESULTS: Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety. CONCLUSIONS: These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABAB receptor signaling in anxiety-associated gating dysregulation.

Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: Study protocol for a double-blind single dummy randomized controlled trial.

BACKGROUND: Smoking is a chronic and relapsing disease, with up to 60% of quitters relapsing within the first year. Transcranial Direct Current Stimulation (tDCS), targets cortical circuits and acutely reduces craving and withdrawal symptoms among cigarette smokers. However, the efficacy of tDCS as an adjunct to standard smoking cessation treatments has not been studied. This study aims to investigate the effectiveness of tDCS in combination with varenicline for smoking cessation. We hypothesize that active tDCS combined with varenicline will improve cessation outcomes compared to sham tDCS combined with varenicline. METHODS: This is a double-blind, sham-controlled randomized clinical trial where fifty healthy smokers will be recruited in Toronto, Canada. Participants will be randomized 1:1 to either active tDCS (20 minutes at 2 mA) or sham tDCS (30 seconds at 2 mA, 19 minutes at 0 mA) for 10 daily sessions (2 weeks) plus 5 follow up sessions, occurring every two weeks for 10 weeks. All participants will be given standard varenicline treatment concurrently for the 12-week treatment period. The primary outcome is 30 day continuous abstinence at end of treatment, confirmed with urinary cotinine. Measurements made at each study visit include expired carbon monoxide, self-reported craving and withdrawal. Three magnetic resonance imaging (MRI) scans will be conducted: two at baseline and one at end of treatment, to assess any functional or structural changes following treatment. DISCUSSION: For every two smokers who quit, one life is saved from a tobacco-related mortality. Therefore, it is important to develop new and more effective treatment approaches that can improve and maintain long-term abstinence, in order to decrease the prevalence of tobacco-related deaths and disease. Furthermore, the addition of longitudinal neuroimaging can shed light on neural circuitry changes that might occur as a result of brain stimulation, furthering our understanding of tDCS in addiction treatment. TRIAL REGISTRATION: This trial has been registered with Clinicaltrials.gov: NCT03841292 since February 15th 2019 (https://clinicaltrials.gov/ct2/show/NCT03841292)-retrospectively registered.

Differences in attentional bias to smoking-related, affective, and sensation-seeking cues between smokers and non-smokers: an eye-tracking study.

RATIONALE: One of the behavioural features of tobacco use disorder is the presence of attentional bias (AB) to smoking-related stimuli. However, much of the research investigating these associations have been limited to the use of reaction-based indices. OBJECTIVES: We aimed to investigate differences in AB to smoking, affective, and sensation-seeking cues in smokers and non-smokers using novel, free-viewing, eye-tracking technology. Secondary aims included investigating impulsivity-by-group interaction effects on AB to sensation-seeking cues. METHODS: Participants were either otherwise-healthy smokers of at least 8 cigarettes per day or otherwise-healthy non-smokers (< 100 cigarettes in their lifetime and no smoking in the past year). AB was measured using a free-viewing, eye-tracking system. Participants were presented a series of slides divided into 3 themes: smoking, affective, and sensation-seeking. Each slide contained 4 images (1 theme-related, 1 neutral, 2 competitive). Primary outcome measure was the difference in the proportion of time spent viewing the theme-related cue to neutral cue. Impulsivity was measured using a monetary delayed discounting task. RESULTS: The sample consisted of 50 smokers (41 ± 12 years old) and 50 age- and sex-matched non-smokers (40 ± 14 years old). Smokers spent over 2 times longer looking at smoking-related images than non-smokers (F = 25.50, p < 0.001). As well, greater impulsivity was significantly associated with increased AB to sensation-seeking cues (R2 = 0.059, F = 2.98, p = 0.04) in smokers but not non-smokers. No differences were found on AB to affective cues. CONCLUSION: The eye-tracking procedure is a sensitive tool for assessing AB in smokers compared to non-smokers to both smoking and sensation-seeking cues.

Lower pro- to anti-inflammatory ratios associated with reduced neurocognitive flexibility in symptomatic adolescents with bipolar disorder.

INTRODUCTION: Peripheral inflammatory markers, such as C-reactive protein (CRP), are elevated among adolescents and adults with bipolar disorder (BD), particularly during symptomatic episodes. Neurocognition, predominantly in the domain of executive function, is also impaired among adults and youth with BD. In adults with BD, CRP is negatively associated with neurocognitive functioning. We aim to investigate this relationship in BD adolescents. METHODS: Serum levels of CRP and five other inflammatory markers (interleukin (IL)-1ß, IL-6, IL-10, IL-4 and tumor necrosis factor α (TNF)) were examined in 60 adolescents with BD (34 symptomatic, 26 asymptomatic) age- and sex-matched to 51 healthy controls (HC). Diagnoses were confirmed using semi-structured interviews. Pro- to anti-inflammatory marker ratios were also examined. Neurocognitive flexibility was assessed via the intra/extradimensional shift (IED) task from the CANTAB battery. Multivariate linear regression controlled for age, sex and race. RESULTS: Within symptomatic BD adolescents, but not asymptomatic BD or HC adolescents, lower IL-6/IL-10 and lower CRP/IL-10 ratios were significantly associated with worse performance on the neurocognitive flexibility task (p = 0.03 and p = 0.04, respectively). Both models accounted for 13.3% of variance in neurocognitive flexibility. No significant CRP by diagnosis interaction effects were observed on neurocognitive flexibility. LIMITATIONS: Limited sample-size restricted ability to separate the symptomatic BD adolescents into varying mood states. CONCLUSION: More balanced pro- to anti-inflammatory ratios were associated with better neurocognitive flexibility in symptomatic BD adolescents. Prospective studies are warranted to assess the direction of these findings.